Leukotriene B4, 5S,12R-dihydroxy-6,8,10,14(Z,E,E,Z)-eicosatetraenoic acid, is a twenty carbon tetra-unsaturated fatty acid and is a relatively unstable molecule. Isotonic aqueous solutions of leukotriene B4 (LTB4) at pH 7.0-7.6, which are suitable for administration to humans and animals are stable for only short periods of time (weeks to months) when stored at temperatures ranging from 2° C. to 25° C. (and above 25° C.). Indeed, LTB4 agents are subject to oxidation, isomerization of double bounds (LTB4 contains two cis and two trans double bounds), epimerization (LTB4 contains two chiral centers), esterification (LTB4 contains a carboxylic group), lactonization, among various possible structural alterations.
LTB4 agents have great pharmaceutical utility, but their use as therapeutic agents in animals or human is problematic, because of their insufficient stability and shelf-life in solution at temperatures between 2° C. to 25° C.
No formulations of solid LTB4 have been reported. Indeed, free LTB4 is known in the art to be an oily substance at room temperature (Kerdesky et al., J. Org. Chem., Vol. 58, 1993, 3516-3520, and U.S. Pat. No. 4,873,024). Kobayashi et al., J. Org. Chem., Vol. 55, 1990, 5324-5335, report a melting point of 25-28° C. for solid leukotriene B4. Crystalline LTB4 has not been reported in the art and no suggestion has been provided of a solid form of LTB4 suitable for solid formulations.
Given the potential of LTB4 agents as therapeutic agents for the prophylaxis and treatment of infections and cancer in humans and animals, it would be highly desirable to provide a novel form of LTB4 suitable for solid pharmaceutical formulations.